EP0130434A1 - Diagnostic test system - Google Patents
Diagnostic test system Download PDFInfo
- Publication number
- EP0130434A1 EP0130434A1 EP84106844A EP84106844A EP0130434A1 EP 0130434 A1 EP0130434 A1 EP 0130434A1 EP 84106844 A EP84106844 A EP 84106844A EP 84106844 A EP84106844 A EP 84106844A EP 0130434 A1 EP0130434 A1 EP 0130434A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- reagents
- antisera
- monoclonal antibodies
- test system
- dried
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
- G01N33/545—Synthetic resin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/80—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
Definitions
- the invention relates to a diagnostic test system consisting of a solid phase made of a protein-binding polystyrene or a polyester film, which is provided on at least one side with a uniform pigment varnish layer adhering to certain reagents, onto which reagents are dried in spatially separated compartments or fields.
- a diagnostic test system is understood to mean, for example, blood group identity cards which are used in particular in the bed side test or microtiter plates for blood group diagnosis which are used in blood group serology, in blood banks, hospitals and in paternity determinations.
- DE-GM 80 29 569 discloses a blood group identity card made of a polyester film provided with a pigmented matting layer, which has dry layers of essentially pure antisera adhering to its surface on spatially separated fields.
- the card described in DE-GM 80 29 569 has the advantage that on the polyester film coated with pigment varnish, as it is on the market as a drawing film , Antisera without any adhesion-promoting additives. This eliminates the need for an adhesive, as was the case with previous cards, and added blood dissolves the dried antisera when stirred, so that it can be dispensed with with water and the test can be carried out very easily and quickly.
- microtiter plate for blood group diagnosis which is equipped with a large number of wells made of a protein-binding plastic and the well bases have firmly adhering dry layers of essentially pure antisera.
- the microtiter plate described in DE-GM 81 37 962 has the advantage that plastic antisera are capable of drying on the rigid, transparent, protein-binding dry Adheres excellently without any adhesion-promoting additives, antisera which are introduced into the wells form a firmly adhering layer on the bottoms of the wells and the layer does not become detached during transport.
- the essentially pure antisera dried on the solid phases are e.g. obtained from citrate plasmas by recalcification.
- the recalcification process is an equilibrium process which does not lead to the complete precipitation of all proteins involved in the coagulation process.
- the invention has for its object to improve the shelf life of diagnostic test systems in which reagents, such as antisera, are dried on a solid phase.
- Monoclonal antibodies are highly specific antibodies which can be produced by immunizing an animal with an antigen, obtaining antibody-producing cells from this animal and the antibody-producing cells with tumor cell lines; e.g. Myeloma cell lines fused to give hybridomas which are isolated and which produce the monoclonal antibodies (Koehler, G. and Milstein, C., Eur.J. Immunol., 6, 511-519 (1976) and Koehler , G. and Milstein, C., Nature, 256, 495 (1975).
- Monoclonal antibodies work like antisera, although they are not part of a serum, but rather “picked” from the serum.
- the monoclonal antibodies obtained from the culture medium of hybridoma cultures in vitro or from the ascites fluids of tumor-bearing host animals react dry to solid phases as agglutinating antibodies in the same way as antisera or immunoglobulin fractions.
- a film material which is particularly suitable for the solid phase is a polyester film which has been produced by the extrusion process and has been made dimensionally stable by biaxial stretching and heat stabilization and is coated on both sides with a uniform matting of pigment lacquer.
- a particularly useful film has the following mechanical and physical properties: tensile strength 1,800 kg / cm 2 , yield strength 980 kg / cm 2 , thermal expansion 0.027 mm / m / ° C, moisture expansion 0.01 mm / m /% RH, heat resistance 150 ° C
- Such a particularly expedient film is commercially available under the name of drawing film Safir PL opaque white.
- the cup bases can be cylindrical, U-shaped or V-shaped.
- Comparative storage tests were carried out between blood group identity cards made of a polyester film, as described above as a particularly expedient film, onto which anti-A and anti-B antisera and on the other hand anti-A and anti-B monoclonal antibodies had been dried.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Selective Calling Equipment (AREA)
Abstract
Description
Die Erfindung betrifft ein diagnostisches Testsystem bestehend aus einer festen Phase aus einem proteinbindungsfähigen Polystyrol oder einer Polyesterfolie, die mindestens auf einer Seite mit einer gleichmäßigen gegenüber bestimmten Reagentien haftfähigen Pigmentlackmattierungsschicht versehen ist, auf die in räumlich voneinander getrennten Kompartinenten oder Feldern Reagentien aufgetrocknet sind.The invention relates to a diagnostic test system consisting of a solid phase made of a protein-binding polystyrene or a polyester film, which is provided on at least one side with a uniform pigment varnish layer adhering to certain reagents, onto which reagents are dried in spatially separated compartments or fields.
Unter diagnostischem Testsystem versteht man beispielsweise Blutgruppenidentitätskarten, die insbesondere ihre Anwendung im Bed side-Test finden oder Mikrotiterplatten zur Blutgruppendiagnostik, die ihre Anwendung in der Blutgruppenserologie, in Blutbanken, Krankenhäusern und bei Vaterschaftsbestimmungen finden.A diagnostic test system is understood to mean, for example, blood group identity cards which are used in particular in the bed side test or microtiter plates for blood group diagnosis which are used in blood group serology, in blood banks, hospitals and in paternity determinations.
Aus dem DE-GM 80 29 569 ist eine Blutgruppenidentitätskarte aus einer mit Pigmentlackmattierungsschicht versehenen Polyesterfolie bekannt, die auf ihrer Oberfläche auf räumlich voneinander getrennten Feldern festhaftende trockne Schichten aus im wesentlichen reinen Antiseren aufweist.DE-GM 80 29 569 discloses a blood group identity card made of a polyester film provided with a pigmented matting layer, which has dry layers of essentially pure antisera adhering to its surface on spatially separated fields.
Gegenüber früheren Blutgruppenidentitätskarten mit angetrockneten Antiseren, die als Haftvermittler Dextran verwendeten, wobei das Dextran-Antiserum-Gemisch nicht direkt mit dem zu testenden Blut vermischt werden konnte, sondern erst mit Wasser aufgelöst werden mußte, hat die in der DE-GM 80 29 569 beschriebene Karte den Vorteil, daß auf der mit Pigmentlackmattierung beschichteten Polyesterfolie, wie sie als Zeichenfolie auf dem Markt ist, Antiseren ohne jegliche haftvermittelnden Zusätze ausgeze ichnet haften. Dadurch entfällt ein Haftmittel, wie es bei früheren Karten erforderlich war, und zugegebenes Blut löst beim Verrühren die angetrockneten Antiseren auf, so daß auf das Auflösen mit Wasser verzichtet werden kann und der Test sehr leicht und schnell durchführbar ist.Compared to previous blood group identity cards with dried antisera, which used dextran as an adhesion promoter, the dextran-antiserum mixture could not be mixed directly with the blood to be tested, but first had to be dissolved with water, the card described in DE-GM 80 29 569 has the advantage that on the polyester film coated with pigment varnish, as it is on the market as a drawing film , Antisera without any adhesion-promoting additives. This eliminates the need for an adhesive, as was the case with previous cards, and added blood dissolves the dried antisera when stirred, so that it can be dispensed with with water and the test can be carried out very easily and quickly.
Aus dem DE-GM 81 37 962 ist eine Mikrotiterplatte zur Blutgruppendiagnostik bekannt, die mit einer Vielzahl von Näpfchen aus einem proteinbindungsfähigen Kunststoff ausgestattet ist und deren Näpfchenböden festhaftende trockne Schichten aus im wesentlichen reinen Antiseren aufweisen.From DE-GM 81 37 962 a microtiter plate for blood group diagnosis is known, which is equipped with a large number of wells made of a protein-binding plastic and the well bases have firmly adhering dry layers of essentially pure antisera.
Gegenüber früheren Mikrotiterplatten, in die flüssige Antiseren entweder unmittelbar vor der Untersuchung in die Näpfchen eingefüllt oder auf Vorrat eingefüllt und eingefroren wurden, hat die in der DE-GM 81 37 962 beschriebene Mikrotiterplatte den Vorteil, daß auf dem starren, transparenten, proteinbindungstrockene fähigen KunststoffVAntiseren ohne jegliche haftvermittelnden Zusätze ausgezeichnet haften, Antiseren, die in die Näpfchen eingebracht werden, eine festhaftende Schicht auf den Böden der Näpfchen bilden und beim Transport kein Ablösender Schicht erfolgt.Compared to earlier microtiter plates, in which liquid antisera were either filled into the wells immediately prior to the examination or filled and frozen in stock, the microtiter plate described in DE-GM 81 37 962 has the advantage that plastic antisera are capable of drying on the rigid, transparent, protein-binding dry Adheres excellently without any adhesion-promoting additives, antisera which are introduced into the wells form a firmly adhering layer on the bottoms of the wells and the layer does not become detached during transport.
Das Einfüllen flüssiger Antiseren entfällt und vor der Anwendung erübrigt sich somit ein Rehydratisieren. Es wird lediglich ein Tropfen Kochsalzaufschwemmung der zu untersuchenden Blute zugegeben, wobei sich durch leichtes Schütteln die Antiseren lösen.There is no need to fill in liquid antisera and rehydration is therefore unnecessary before use. Only a drop of saline suspension is added to the blood to be examined, and the antisera dissolve by shaking gently.
Nach kurzem Zentrifugieren (z.B. 2 Minuten bei 1000 U/Min.) - ohne vorausgehende Inkubation - wird aufgeschüttelt und ausgewertet.After a short centrifugation (e.g. 2 minutes at 1000 rpm) - without previous incubation - the mixture is shaken and evaluated.
Neben all den Vorteilen, die diese vorstehend beschriebenen diagnostischen Testsysteme gegenüber früheren Systemen aufweisen, besitzen sie jedoch den Nachteil, daß ihre Lagerfähigkeit bei höheren Temperaturen oder bei der sogenannten Wechsellagerung, d.h. Wechsel zwischen höheren und niedrigeren Temperaturen begrenzt ist.In addition to all the advantages that these diagnostic test systems described above have over previous systems, they have the disadvantage, however, that their shelf life at higher temperatures or during so-called alternate storage, i.e. Alternation between higher and lower temperatures is limited.
Die auf den festen Phasen angetrockneten, im wesentlichen reinen Antiseren werden z.B. aus Citratplasmen durch Rekalzifizierung gewonnen. Der Rekalzifizierungsvorgang ist ein Gleichgewichtsprozeß, der nicht zur völligen Ausfällung aller am Gerinnungsvorgang beteiligter Proteine führt.The essentially pure antisera dried on the solid phases are e.g. obtained from citrate plasmas by recalcification. The recalcification process is an equilibrium process which does not lead to the complete precipitation of all proteins involved in the coagulation process.
Um Denaturierung der Proteine zu verhindern, muß eine gewisse Restfeuchte im Produkt vorhanden sein. Bei Lagerung bei höheren Temperaturen finden in Gegenwart der Restfeuchte Wechselwirkungen der Proteine untereinander statt, die zu Gelbildung führen. Die Vielfalt der Proteine und ihre Wechselwirkungen untereinander machen es unmöglich, genaue Angaben über schwerlösliche oder zur Gelbildung führende Proteine zu machen. Als störende Faktoren kommen vor allem Denaturierungs- und Abbauprodukte der am Gerinnungsablauf beteiligten Proteine in Betracht. Der Faktor XIII, ein fibrinstabilisierender Gerinnungsfaktor, kann zu Quervernetzungen führen, und es ist mit Fibronectin, dem CIG (cold insoluble globulin), einem Fibrinabbauprodukt, zu rechnen, das bei Zimmertemperatur nicht in Lösung geht.In order to prevent denaturation of the proteins, a certain residual moisture must be present in the product. When stored at higher temperatures, the proteins interact with each other in the presence of the residual moisture, which leads to gel formation. The variety of proteins and their interactions make it impossible to give precise information about poorly soluble or gel-forming proteins. Denaturing and degradation products of the proteins involved in the coagulation process are particularly disruptive factors. Factor XIII, a fibrin-stabilizing coagulation factor, can lead to cross-linking, and fibronectin, the CIG (cold insoluble globulin), a fibrin breakdown product, is to be expected at room temperature does not go into solution.
Bei Zugabe von Blut oder einer Erythrozytensuspension zu den angetrockneten Antiseren kann eine solche Gelbildung ein vollständiges Auflösen verhindern, was zu falsch positiven Resultaten führt, da die Gelbildung wie eine Agglutination aussieht.If blood or an erythrocyte suspension is added to the dried antisera, such gel formation can prevent complete dissolution, which leads to false positive results, since the gel formation looks like agglutination.
Der Erfindung liegt die Aufgabe zugrunde, die Lagerfähigkeit diagnostischer Testysteme, bei denen auf eine feste Phase Reagentien, wie Antiseren, aufgetrocknet sind, zu verbessern.The invention has for its object to improve the shelf life of diagnostic test systems in which reagents, such as antisera, are dried on a solid phase.
Diese Aufgabe wird erfindungsgemäß dadurch gelöst, daß in einem gattungsgemäßen diagnostischen Testystem als aufgetrocknete Reagentien anstelle herkömmlicher Antiseren oder deren Immunglobulin-Fraktionen, monoklonale Antikörper mit Spezifität gegen bestimmte Antigene, insbesondere Blutgruppenantigene, verwendet werden.This object is achieved in that in a generic diagnostic test system as dried reagents instead of conventional antisera or their immunoglobulin fractions, monoclonal antibodies with specificity against certain antigens, in particular blood group antigens, are used.
Man fand, daß aufgrund der Reinheit der monoklonalen Antikörper - sie sind praktisch frei von Fremdproteinen - keine Nachgerinnung oder störende Gelbildung bei Lagerung bei höheren Temperaturen oder Raumtemperatur stattfindet.It was found that due to the purity of the monoclonal antibodies - they are practically free of foreign proteins - there is no post-clotting or disruptive gel formation when stored at higher temperatures or room temperature.
Gegen die Verwendung von monoklonalen Antikörpern für den erfindungsgemäßen Zweck bestand jedoch ein Vorurteil. Es zwar zu erwarten, daß aufgrund der hohen Verdünnung, in der monoklonale Antikörper vorliegen, und der Abwesenheit von Schutzkolloiden, wie z.B. Albumin, keine lange Haltbarkeit besonders bei Raumtemperatur oder höherer Temperatur vorhanden sein würde, da bekanntlich hochverdünnte Proteinlösungen, in denen durch die Verdünnung auch der kolloidale Schutzfaktor verringert wird, äußerst instabil sind.However, there was a prejudice against the use of monoclonal antibodies for the purpose according to the invention. It can be expected that due to the high dilution in which monoclonal antibodies are present and the absence of protective colloids, such as Albumin, there would be no long shelf life, especially at room temperature or higher temperature, since it is known that highly diluted protein solutions, in which the colloidal protective factor is also reduced by the dilution, are extremely unstable.
Überraschenderweise zeigte sich jedoch, daß bei der erfindungsgemäßen Verwendung monoklonale Antikörper außergewöhnlich stabil und lange reaktionsfähig sind.Surprisingly, however, it was found that monoclonal antibodies are extraordinarily stable and reactive for a long time when used according to the invention.
Monoklonale Antikörper sind hochspezifische Antikörper, die sich dadurch herstellen lassen, daß man ein Tier mit einem Antigen immunisiert, Antikörper produzierende Zellen von diesem Tier erhält und die Antikörper produzierenden Zellen mit Tumor-Zell-Linien; z.B. Myeloma-Zell-Linien, fusioniert, wobei man Hybridomas erhält, die isoliert werden und die die monoklonalen Antikörper produzieren (Köhler, G. und Milstein, C., Eur.J.Immunol., 6, 511-519 (1976) und Köhler, G. und Milstein, C., Nature, 256, 495 (1975) .Monoclonal antibodies are highly specific antibodies which can be produced by immunizing an animal with an antigen, obtaining antibody-producing cells from this animal and the antibody-producing cells with tumor cell lines; e.g. Myeloma cell lines fused to give hybridomas which are isolated and which produce the monoclonal antibodies (Koehler, G. and Milstein, C., Eur.J. Immunol., 6, 511-519 (1976) and Koehler , G. and Milstein, C., Nature, 256, 495 (1975).
Monoklonale Antikörper funktionieren wie Antiseren, obgleich sie nicht Bestandteil eines Serums, sondern aus dem Serum "herausgepickte" Antikörper sind.Monoclonal antibodies work like antisera, although they are not part of a serum, but rather "picked" from the serum.
Die aus dem Kulturmedium von Hybridoma-Kulturen in vitro oder aus den Ascitesflüssigkeiten von tumortragenden Wirtstieren gewonnenen monoklonalen Antikörper reagieren angetrocknet auf festen Phasen als agglutinierende Antikörper in gleicher Weise wie Antiseren oder Immunglobulin-Fraktionen.The monoclonal antibodies obtained from the culture medium of hybridoma cultures in vitro or from the ascites fluids of tumor-bearing host animals react dry to solid phases as agglutinating antibodies in the same way as antisera or immunoglobulin fractions.
Sie haften auf den erfindungsgemäß zu verwendeten festen Phasen ohne jegliche haftvermittelnden Zusätze in genauso ausgezeichneter Weise wie Antiseren.They adhere to the solid phases to be used according to the invention without any adhesion-promoting additives in the same excellent way as antisera.
Ein für die feste Phase besonders geeignetes Folienmaterial ist eine Polyesterfolie, die im Extrudierverfahren hergestellt und durch biaxiale Streckung und Hitzestabilisierung dimensionsstabil gemacht wurde und auf beiden Seiten mit einer gleichmäßigen Pigmentlackmattierung beschichtet ist. Eine besonders zweckmäßige Folie besitzt folgende mechanische und physikalische Eigenschaften: Zugfestigkeit 1 800 kg/cm2, Streckgrenze 980 kg/cm2, thermische Ausdehnung 0,027 mm/m/°C, Feuchtigkeitsausdehnung 0,01 mm/m/% RF, Wärmefestigkeit 150°C Eine derart besonders zweckmäßige Folie ist unter der Bezeichnung Zeichenfolie Safir PL Opak-weiß im Handel erhältlich.A film material which is particularly suitable for the solid phase is a polyester film which has been produced by the extrusion process and has been made dimensionally stable by biaxial stretching and heat stabilization and is coated on both sides with a uniform matting of pigment lacquer. A particularly useful film has the following mechanical and physical properties: tensile strength 1,800 kg / cm 2 , yield strength 980 kg / cm 2 , thermal expansion 0.027 mm / m / ° C, moisture expansion 0.01 mm / m /% RH, heat resistance 150 ° C Such a particularly expedient film is commercially available under the name of drawing film Safir PL opaque white.
Als besonders gut geeignete Mikrotiterplatten erwiesen sich Flachbodenplatten mit zylindrischen Näpfchen aus strahlensterilisiertem Polystyrol, wie sie für die Verwendung für Zellkulturen im Costar (R) Kat.Nr. 3596 beschrieben werden. Diese Platten weisen eine hohe Proteinbindungsfähigkeit auf. Die Näpfchen- bö.den können zylindrisch, U-förmig oder V-förmig ausgebildet sein.Flat-bottom plates with cylindrical wells made of radiation-sterilized polystyrene, such as those used for cell cultures in Costar (R) Cat.No. 3596 can be described. These plates have a high protein binding capacity. The cup bases can be cylindrical, U-shaped or V-shaped.
Es wurden vergleichende Lagerungsversuche zwischen Blutgruppenidentitätskarten aus einer Polyesterfolie, wie sie vorstehend als besonders zweckmäßige Folie beschrieben wurde durchgeführt, auf die einerseits Anti-A und Anti-B Antiseren und andererseits Anti-A und Anti-B monoklonale Antikörper aufgetrocknet worden waren.Comparative storage tests were carried out between blood group identity cards made of a polyester film, as described above as a particularly expedient film, onto which anti-A and anti-B antisera and on the other hand anti-A and anti-B monoclonal antibodies had been dried.
Bei einer Wechsellagerung zwischen 37°C und 2-8°C war bei den mit Antiseren beschichteten Karten bereits nach 3 Wochen Gelbildung zu beobachten, während bei den mit monoklonalen Antikörpern beschichteten Karten nach 14 Wochen keine Gelbildung erfolgt war und die Antikörper völlig intakt bzw. reaktiv waren ohne störende Effekte.With alternating storage between 37 ° C and 2-8 ° C, the gel coated with antisera was observed after 3 weeks, whereas with cards coated with monoclonal antibodies no gel was formed after 14 weeks and the antibodies were completely intact or were reactive without disruptive effects.
Man verfuhr nach Beispiel 1, jedoch mit dem Unterschied, daß man die Karten bei Raumtemperatur lagerte. Bei den mit Antiseren beschichteten Karten war bereits nach 6 Wochen Gelbildung zu beobachten, während bei den mit monoklonalen Antikörpern beschichteten Karten nach 27 Wochen keine Gelbildung erfolgt war und die Antikörper völlig intakt bzw. reaktiv waren ohne störende Effekte.The procedure was as in Example 1, but with the difference that the cards were stored at room temperature. In the case of cards coated with antisera, gel formation was observed after only 6 weeks, while in the case of cards coated with monoclonal antibodies, no gel formation had occurred after 27 weeks and the antibodies were completely intact or reactive without disruptive effects.
Außer zur Blutgruppenbestimmung lassen sich mit dem erfindungsgemäßen Testsystem auch andere serologische und mikrobiologische Tests durchführen.In addition to blood group determination, other serological and microbiological tests can also be carried out with the test system according to the invention.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT84106844T ATE27494T1 (en) | 1983-07-01 | 1984-06-15 | DIAGNOSTIC TEST SYSTEM. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE3323645 | 1983-07-01 | ||
DE19833323645 DE3323645A1 (en) | 1983-07-01 | 1983-07-01 | DIAGNOSTIC TEST SYSTEM |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0130434A1 true EP0130434A1 (en) | 1985-01-09 |
EP0130434B1 EP0130434B1 (en) | 1987-05-27 |
Family
ID=6202820
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP84106844A Expired EP0130434B1 (en) | 1983-07-01 | 1984-06-15 | Diagnostic test system |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0130434B1 (en) |
JP (1) | JPS6036965A (en) |
AT (1) | ATE27494T1 (en) |
DE (2) | DE3323645A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2573873A1 (en) * | 1984-11-23 | 1986-05-30 | Human Oltoanyagtermelo | FAST DIAGNOSTIC MEANS FOR BLOOD GROUPING AND PROCESS FOR PREPARING THE SAME |
EP0232706A2 (en) * | 1986-01-10 | 1987-08-19 | Sloan-Kettering Institute For Cancer Research | Blood group antigen panel |
WO1988007201A1 (en) * | 1987-03-13 | 1988-09-22 | Tanox Biosystems, Inc. | Antibody matrix device |
EP0331808A1 (en) * | 1988-01-28 | 1989-09-13 | Biotest AG | Immunoassay method to determine blood groups |
EP0350233A2 (en) * | 1988-07-05 | 1990-01-10 | Immucor, Inc. | An article for performing immunological assays utilizing organic dyes and methods for producing and utilizing same |
US6265176B1 (en) * | 1985-10-29 | 2001-07-24 | Cordis Corporation | Dot immunoassay on plastic sheets |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3341518C1 (en) * | 1983-11-17 | 1985-04-18 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | Method and device for applying a test reagent to a diagnostic test card |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0051748A1 (en) * | 1980-11-06 | 1982-05-19 | Biotest-Serum-Institut GmbH | Blood group identification card, particularly for the bed side test |
DE3145007A1 (en) * | 1981-11-12 | 1983-05-19 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | IMMOBILIZED BIOLOGICALLY ACTIVE SUBSTANCES AND THEIR USE |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4211602A (en) * | 1978-05-04 | 1980-07-08 | Brumfield Robert C | Surface treatment for blood dialysis cartridges |
US4329317A (en) * | 1981-01-29 | 1982-05-11 | Smithkline Instruments, Inc. | Method of stabilizing a specimen slide for occult blood testing |
JPS57136165A (en) * | 1981-02-18 | 1982-08-23 | Mochida Pharmaceut Co Ltd | Immunological measuring reagent |
DE8137962U1 (en) * | 1981-12-28 | 1982-06-16 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | MICROTITER PLATE FOR BLOOD GROUP DIAGNOSTICS |
-
1983
- 1983-07-01 DE DE19833323645 patent/DE3323645A1/en not_active Ceased
-
1984
- 1984-06-15 AT AT84106844T patent/ATE27494T1/en not_active IP Right Cessation
- 1984-06-15 DE DE8484106844T patent/DE3463975D1/en not_active Expired
- 1984-06-15 EP EP84106844A patent/EP0130434B1/en not_active Expired
- 1984-07-02 JP JP59135344A patent/JPS6036965A/en active Granted
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0051748A1 (en) * | 1980-11-06 | 1982-05-19 | Biotest-Serum-Institut GmbH | Blood group identification card, particularly for the bed side test |
DE3145007A1 (en) * | 1981-11-12 | 1983-05-19 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | IMMOBILIZED BIOLOGICALLY ACTIVE SUBSTANCES AND THEIR USE |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2573873A1 (en) * | 1984-11-23 | 1986-05-30 | Human Oltoanyagtermelo | FAST DIAGNOSTIC MEANS FOR BLOOD GROUPING AND PROCESS FOR PREPARING THE SAME |
AT390845B (en) * | 1984-11-23 | 1990-07-10 | Human Oltoanyagtermelo | QUICK DIAGNOSTICS FOR BLOOD GROUP DETERMINATION |
US6265176B1 (en) * | 1985-10-29 | 2001-07-24 | Cordis Corporation | Dot immunoassay on plastic sheets |
EP0232706A2 (en) * | 1986-01-10 | 1987-08-19 | Sloan-Kettering Institute For Cancer Research | Blood group antigen panel |
EP0232706A3 (en) * | 1986-01-10 | 1988-11-30 | Sloan-Kettering Institute For Cancer Research | Blood group antigen panel |
WO1988007201A1 (en) * | 1987-03-13 | 1988-09-22 | Tanox Biosystems, Inc. | Antibody matrix device |
EP0331808A1 (en) * | 1988-01-28 | 1989-09-13 | Biotest AG | Immunoassay method to determine blood groups |
EP0350233A2 (en) * | 1988-07-05 | 1990-01-10 | Immucor, Inc. | An article for performing immunological assays utilizing organic dyes and methods for producing and utilizing same |
EP0350233A3 (en) * | 1988-07-05 | 1990-11-22 | Immucor, Inc. | An article for performing immunological assays utilizing organic dyes and methods for producing and utilizing same |
US5468618A (en) * | 1988-07-05 | 1995-11-21 | Immucor, Inc. | Article for performing immunological assays utilizing organic dyes to immobilize immunologically reactive components to a solid phase support and methods for producing and utilizing same |
Also Published As
Publication number | Publication date |
---|---|
DE3323645A1 (en) | 1985-01-10 |
EP0130434B1 (en) | 1987-05-27 |
DE3463975D1 (en) | 1987-07-02 |
JPS6036965A (en) | 1985-02-26 |
ATE27494T1 (en) | 1987-06-15 |
JPH0562303B2 (en) | 1993-09-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0084102B1 (en) | Microtitration plate for blood group diagnosis | |
Poole et al. | Association of an extracellular protein (chondrocalcin) with the calcification of cartilage in endochondral bone formation. | |
Chen et al. | Identification of the cold-insoluble globulin of plasma in amniotic fluid | |
EP0944832B1 (en) | ANTIGEN-SPECIFIC IgM DETECTION | |
DE19524572A1 (en) | Method for producing a synthetic calibrator for use in immunoassays, consisting of the analytes or partial sequences thereof, which are conjugated to inert carrier molecules | |
DE2546379A1 (en) | IMMOBILIZED BIOLOGICALLY ACTIVE SUBSTANCE AND THEIR USE | |
EP0130434B1 (en) | Diagnostic test system | |
DE69435072T2 (en) | ANTIBODY AGAINST HUMAN SOLUBLE FIBRIN, HYBRIDOME THAT YOU PRODUCE AND IMMUNE MEASUREMENT PROCEDURE | |
DE2134928B2 (en) | Immunological reagent and process for its preparation | |
DE3218312C2 (en) | Monoclonal antibodies, hybridoma cell clones, process for their preparation and their use for the detection of breast cancer and malignant lymphogranulomatosis | |
Kornguth et al. | ISOLATION OF SYNAPTIC COMPLEXES IN A CAESIUM CHLORIDE DENSITY GRADIENT: ELECTRON MICROSCOPIC AND IMMUNOHISTOCHEMICAL STUDIES 1 | |
DE3500190A1 (en) | IMPROVED TEST COMPOSITIONS, METHODS FOR THEIR PRODUCTION AND THEIR USE IN TEST PROCEDURES | |
EP0211229A2 (en) | Coated carriers for the binding of bio-affinative substances | |
EP0008720A1 (en) | Diagnostic agent and method for the detection of mitochondrial or nuclear antibodies | |
CH630643A5 (en) | Process for concentrating a placenta-specific glycoprotein. | |
US2761811A (en) | Preparation of blood fraction for use in rh testing procedures | |
EP0331808B1 (en) | Immunoassay method to determine blood groups | |
EP0134025A1 (en) | Macromolecular compositions including chemically active fillers, process for their production and their use | |
CH636449A5 (en) | Method for obtaining a new specific alpha-l-antikoerpers. | |
EP0529348B1 (en) | Process for the purification of factor XIII, monoclonal antibodies against factor XIIIA, preparation and use thereof | |
JPH0228556A (en) | Manufacture of particle stabilizing epitope for standardization and control of immunological test | |
DE2733380A1 (en) | Immunological assay using carrier bound reactant - incubated with second reactant and then with labelled reactant specific for the second | |
DE69735760T2 (en) | ANTIBODIES TO HUMAN LECT2, CELLS THAT PRODUCE AND METHOD AND KIT AT ITS DETERMINATION | |
DE3721790A1 (en) | Cartilage cell-specific membrane proteins and method for the diagnosis and progress control of autoimmune reactions against cartilage cells | |
DE19528847C2 (en) | Affinity chromatographic method for the detection of antigens and / or antibodies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
17P | Request for examination filed |
Effective date: 19850416 |
|
17Q | First examination report despatched |
Effective date: 19861023 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
ITF | It: translation for a ep patent filed |
Owner name: ING. A. GIAMBROCONO & C. S.R.L. |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
REF | Corresponds to: |
Ref document number: 27494 Country of ref document: AT Date of ref document: 19870615 Kind code of ref document: T |
|
REF | Corresponds to: |
Ref document number: 3463975 Country of ref document: DE Date of ref document: 19870702 |
|
ET | Fr: translation filed | ||
BECN | Be: change of holder's name |
Effective date: 19870527 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PFA Free format text: BIOTEST AKTIENGESELLSCHAFT |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed | ||
REG | Reference to a national code |
Ref country code: FR Ref legal event code: CN |
|
NLS | Nl: assignments of ep-patents |
Owner name: BIOTEST AKTIENGESELLSCHAFT TE FRANKFORT A.D. MAIN, |
|
BECN | Be: change of holder's name |
Effective date: 19880114 |
|
ITTA | It: last paid annual fee | ||
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 19930512 Year of fee payment: 10 |
|
EPTA | Lu: last paid annual fee | ||
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19940615 |
|
EAL | Se: european patent in force in sweden |
Ref document number: 84106844.8 |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: IF02 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 20030604 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20030610 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20030611 Year of fee payment: 20 Ref country code: AT Payment date: 20030611 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 20030616 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20030626 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20030630 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20030902 Year of fee payment: 20 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20040614 Ref country code: GB Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20040614 Ref country code: CH Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20040614 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20040615 Ref country code: AT Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20040615 |
|
BE20 | Be: patent expired |
Owner name: *BIOTEST A.G. Effective date: 20040615 |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: PE20 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
NLV7 | Nl: ceased due to reaching the maximum lifetime of a patent |
Effective date: 20040615 |
|
EUG | Se: european patent has lapsed |